Other highlights in the March 3 issue of JNCI

People who had hereditary retinoblastoma during childhood and did not receive high-dose radiation therapy to treat their cancer are nevertheless at an increased risk of epithelial cancers such as cancer of the esophagus, stomach, colon, lung, breast, cervix, or prostate.

Retinoblastoma is a rare childhood tumor of one or both eyes. The tumor can be sporadic or hereditary, the latter of which is associated in a mutation in the retinoblastoma 1 (RB1) gene. Compared with the general population, survivors of hereditary retinoblastoma have higher risks of early-onset second cancers, particularly sarcomas, brain tumors, and melanoma, and that risk is strongly associated with the amount of radiation received during retinoblastoma treatment. However, there is little information available about cancer risk later in life among retinoblastoma survivors--specifically, cancers that are likely not related to radiotherapy.

Olivia Fletcher and Julian Peto, of the London School of Hygiene and Tropical Medicine, and colleagues estimated the risks of the epithelial cancers that commonly occur after age 50 among 144 retinoblastoma survivors who were unlikely to have been treated with high-dose radiotherapy.

They found that very few of the cancers diagnosed within their cohort were bone or soft tissue cancers, in contrast to findings from contemporary studies in which patients are treated with radiotherapy and are more likely to have sarcomas as their second cancers. Compared with the general population, the retinoblastoma survivors were more likely to die of lung cancer, bladder cancer, and all other epithelial cancers combined.

Dietary Folate Intake May Be Associated With Reduced Risk of Ovarian Cancer

A high intake of dietary folate may be associated with a lower risk of ovarian cancer, especially among women who consume alcohol.

Folate is a water-soluble B vitamin that has been shown to play an important role in DNA synthesis and repair. Previous studies have shown that a low intake of folate may be associated with an increased risk of breast and colorectal cancer, especially among alcohol drinkers. Susanna Larsson and Alicja Wolk of the Karolinska Institute in Stockholm and Edward Giovannucci of the Harvard School of Public Health examined data from 61,084 women in the Swedish Mammography Cohort to examine the association between dietary folate intake (i.e., folate from food sources) and the incidence of epithelial ovarian cancer.

They found that dietary folate intake was weakly inversely associated with epithelial ovarian cancer risk. Among women who consumed more than 20 g of alcohol per week (approximately two alcoholic drinks), women with the highest dietary folate intake had a 74% lower risk of epithelial ovarian cancer compared with those with the lowest folate intake. There was no association between dietary folate intake and ovarian cancer risk among women who consumed 20 g or less of alcohol per week.

"Additional studies are needed to determine the generalizability of our results to other populations that have higher folate intakes and to evaluate the efficacy and safety of high doses of folate from supplements with respect to cancer," the authors write.

Intake of dietary heme iron--the type of iron found in meat--is associated with an increased risk of proximal colon cancer, especially among women who drink alcohol, a new study has found. However, intake of dietary zinc, which is most abundant in the same foods that have a high amount of heme iron, is associated with a decreased risk of both proximal and distal colon cancer.

The association between iron intake and colon cancer risk is unclear. Most of the data examining such an association comes from epidemiologic studies, most of which look only at total dietary iron intake. In addition, the effect of iron in the body may be affected by alcohol consumption. Kristin E. Anderson of the University of Minnesota School of Public Health and colleagues examined associations among colon cancer incidence and dietary intake of heme iron, zinc, and alcohol. They looked at 15 years of follow-up data on 34,708 postmenopausal women ages 55 to 69 who completed a food-frequency questionnaire for the Iowa Women's Health Study.

The authors found that the relative risks for proximal colon cancer increased more than twofold across categories of heme iron intake and the corresponding relative risks decreased more than 50% across categories for zinc intake. The positive association with heme iron and the inverse association with zinc intake were stronger among women who consumed alcohol than among those who did not. Zinc intake was also associated with a decreased risk of distal colon cancer, regardless of alcohol or heme iron consumption.

"Our results may explain, at least in part, inconsistent findings with respect to the role of meat consumption in colon cancer," the authors write.

Serum Proteomic Patterns for Diagnosing Cancer: Recent reports about using protein patterns in serum to diagnose ovarian and prostate cancers have generated much excitement about the potential future applicability of such analyses. In a Commentary, Eleftherios P. Diamandis of Mount Sinai Hospital in Toronto summarizes some of the shortcomings of one technique used to analyze serum proteomic patterns, surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. He explains why he thinks it is unlikely that SELDI-TOF will be a useful approach for the diagnosis of cancer. He identifies artifacts that could bias data obtained using this technology and he suggests that the technique may identify molecules whose serum concentrations vary considerably because of factors such as acute or chronic inflammatory conditions. He concludes that SELDI-TOF should not be used in clinical practice until the methodology is standardized for at least one or two cancers.

Connective Tissue Growth Factor Invasion and Metastasis: Connective tissue growth factor (CTGF) is a secreted protein that binds to integrins and modulates the invasive behavior of certain human cancer cells. Cheng-Chi Chang, of National Taiwan University, and colleagues investigated the roles of CTGF and its possible downstream effector collapsin response mediator protein 1 (CRMP-1) in invasion and metastasis in cells from human lung adenocarcinoma, a cancer that is known to metastasize quickly. They conclude that CTGF inhibits metastasis and invasion of human lung adenocarcinoma by a CRMP-1–dependent mechanism.

Insulin-Like Growth Factor-II and Colorectal Cancer: A genetic change called loss of imprinting (LOI) of insulin-like growth factor-II (IGF-II) may be an inherited epigenetic trait that may predispose an individual to colorectal cancer. Karen Woodson, of the National Cancer Institute, and colleagues evaluated the association between LOI of IGF-II in normal colonic mucosal samples and adenomas in women participating in a colonoscopy screening study. The authors conclude that their findings support the hypothesis that LOI of IGF-II is an epigenetic trait polymorphic in the population and suggest that LOI of IGF-II may play a role in colorectal cancer.